Abstract
Peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutic agents. The type and degree of neuropathy depend on the chemotherapy drug, dose-intensity, and cumulative dose. Disabling peripheral neuropathy has a significant negative impact on quality of life. Accordingly, a reliable assessment of chemotherapy-induced peripheral neurotoxicity is necessary, especially if potential neuroprotective agents are to be investigated. Chemoprotectants are agents that have been developed to ameliorate the toxicity associated with cytotoxic drugs. They aim to provide site-specific protection for normal tissues, without compromising antitumor efficacy. Several chemoprotectant compounds have been studied in recent clinical trials. These trials must include sufficient dose-limiting events for study and assessment of both toxicity and antitumor effect. A future avenue of investigation includes the identification of patients at higher risk for the development of peripheral neuropathy based on their genotype. Identification of these higher-risk patients may enable us to devise prevention strategies prior to the onset of this potentially debilitating complication.
Similar content being viewed by others
References
Ajani JA, Welch SR, Raber MNet al (1990) Comprehensive criteria for assessing therapy-induced toxicity. Cancer Invest 8:47–59
Apfel SC (2000) Managing the neurotoxicity of paclitaxel (Taxol) and docetaxel (Taxotere) with neurotrophic factors. Cancer Invest 18:564–573
Barohn RJ (1998) Approach to peripheral neuropathy and neuronopathy. Semin Neurol 18:7–18
Capizzi RL (1999) The preclinical basis for broad-spectrum selective cytoprotection of normal tissues from cytotoxic therapies by amifostine. Semin Oncol 26:3–21
Cascinu S, Catalano V, Cordella L et al (2002) Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 20:3478–3483
Cascinu S, Cordella L, Del Ferro E et al (1995) Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J Clin Oncol 13:26–32
Casey EB, Fullerton PM, Jelliffe AW (1970) Vincristine neurotoxicity: a clinical and electrophysiological study of eighteen patients. Clin Sci 38:23P–24P
Casey EB, Jellife AM, Le Quesne PM, Millett YL (1973) Vincristine neuropathy. Clinical and electrophysiological observations. Brain 96:69–86
Chaudhry V, Chaudhry M, Crawford TO et al (2003) Toxic neuropathy in patients with pre-existing neuropathy. Neurology 60:337–340
Chaudhry V, Rowinsky EK, Sartorius SE et al (1994) Peripheral neuropathy from taxol and cisplatin combination chemotherapy: clinical and electrophysiological studies. Ann Neurol 35:304–311
Chaudhry V, Cornblath DR, Corse A et al (2002) Thalidomide-induced neuropathy. Neurology 59:1872–1875
Colombo N, Bini S, Miceli D et al (1995) Weekly cisplatin ± glutathione in relapsed ovarian carcinoma. Int J Gynecol Cancer 5:81–86
De Vos F (2003) A randomized phase II study of paclitaxel (P) with carboplatin (C) ± amifostine (A) as first line treatment in advanced ovarian carcinoma. Proc Amer Soc Clin Oncol 22:448
Extra JM, Espie M, Calvo F et al (1990) Phase I study of oxaliplatin in patients with advanced cancer. Cancer Chemother Pharmacol 25:299–303
Extra JM, Marty M, Brienza S, Misset JL (1998) Pharmacokinetics and safety profile of oxaliplatin. Semin Oncol 25:13–22
Fischer SJ, Podratz JL, Windebank AJ (2001) Nerve growth factor rescue of cisplatin neurotoxicity is mediated through the high affinity receptor: studies in PC12 cells and p75 null mouse dorsal root ganglia. Neurosci Lett 308:1–4
Gelmon K, Eisenhauer E, Bryce C et al (1999) Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer. J Clin Oncol 17:3038–3047
Gibbels E, Scheid W, Wieck HH, Kinzel W (1973) [Thalidomide neuropathy in the late stage. A clinical documentation]. Fortschr Neurol Psychiatr Grenzgeb 41:378–417
Hafstrom T (1967) Polyneuropathy after neurosedyn (thalidomide) and its prognosis. Acta Neurol Scand 43 [Suppl32]:1–41
Hildebrandt G, Holler E, Woenkhaus M et al (2000) Acute deterioration of Charcot-Marie-Tooth disease IA (CMT IA) following 2 mg of vincristine chemotherapy. Ann Oncol 11:743–747
Hilpert F (2003) Neuroprotection with amifostine in 1st-line treatment of advanced ovarian cancer with carboplatin/taxane-based chemotherapy-a double-blind, placebo-controlled, randomized phase II-study of the AGO Ovarian Cancer Study Group. Proc Amer Soc Clin Oncol 22:448
Hovestadt A, van der Burg ME, Verbiest HB et al (1992) The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo. J Neurol 239:143–146
Igarashi M, Thompson EI, Rivera GK (1995) Vincristine neuropathy in type I and type II Charcot-Marie-Tooth disease (hereditary motor sensory neuropathy). Med Pediatr Oncol 25:113–116
Jacobson S, Loprinzi C (2002) Glutamine for preventing paclitaxel-associated malgias and arthralgias: unfortunately a “no go.” Proc Amer Soc Clin Oncol 1460
Kemp G, Rose P, Lurain J et al (1996) Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 14:2101–2112
Klimberg VS, McClellan JL (1996) Claude H. Organ, Jr. Honorary Lectureship. Glutamine, cancer, and its therapy. Am J Surg 172:418–424
Lee RT, Oster MW, Balmaceda C et al (1999) Bilateral facial nerve palsy secondary to the administration of high-dose paclitaxel. Ann Oncol 10:1245–1247
Links M, Lewis C (1999) Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs 57:293–308
Ma W, Eisenach JC (2002) Morphological and pharmacological evidence for the role of peripheral prostaglandins in the pathogenesis of neuropathic pain. Eur J Neurosci 6:1037–1047
Maestri A (2002) Acetyl-L-carnitine (ALCAR) in patients with chemotherapy-induced peripheral sensory neuropathy. Proc Amer Soc Clin Oncol 2807
McDonald ES, Windebank AJ (2002) Cisplatin-induced apoptosis of DRG neurons involves bax redistribution and cytochrome c release but not fas receptor signaling. Neurobiol Dis 9:220–233
Miller AB, Hoogstraten B, Staquet M, Winkler A (1981) Reporting results of cancer treatment. Cancer, 47:207–214
Nakamura Y, Shimizu H, Nishijima C et al (2001) Delayed functional recovery by vincristine after sciatic nerve crush injury: a mouse model of vincristine neurotoxicity. Neurosci Lett 304:5–8
Nozaki-Taguchi N, Chaplan SR, Higuera ES, et al (2001) Vincristine-induced allodynia in the rat. Pain 93:69–76
Oken MM, Creech RH, Tormey DCet al (1982) Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649–655
Parnis FX, Coleman RE, Harper PG et al (1995) A randomised double-blind placebo controlled clinical trial assessing the tolerability and efficacy of glutathione as an adjuvant to escalating doses of cisplatin in the treatment of advanced ovarian cancer. Eur J Cancer 31A:1721
Peltier AC, Russell JW (2002) Recent advances in drug-induced neuropathies. Curr Opin Neurol 15:633–638
Postma TJ, Heimans JJ (2000) Grading of chemotherapy-induced peripheral neuropathy. Ann Oncol 11:509–513
Postma TJ, Heimans JJ, Muller MJ et al (1998) Pitfalls in grading severity of chemotherapy-induced peripheral neuropathy. Ann Oncol 9:739–744
Quasthoff S, Hartung HP (2002) Chemotherapy-induced peripheral neuropathy. J Neurol, 249, 9–17
Raymond, E,Faivre, S,Woynarowski, JM,Chaney, SG (1998) Oxaliplatin: mechanism of action and antineoplastic activity. Semin Oncol 25:4–12
Rowinsky EK, Eisenhauer EA, Chaudhry V et al (1993) Clinical toxicities encountered with paclitaxel (Taxol). Semin Oncol 20:1–15
Russell JW, Windebank AJ, McNiven MA et al (1995) Effect of cisplatin and ACTH4–9 on neural transport in cisplatin induced neurotoxicity. Brain Res 676:258–267
Santini V (2001) Amifostine: chemotherapeutic and radiotherapeutic protective effects. Expert Opin Pharmacother 2:479–489
Savarese D, Boucher J, Corey B (1998) Glutamine treatment of paclitaxel-induced myalgias and arthralgias. J Clin Oncol 16:3918–3919
Schiller JH, Storer B, Tutsch K et al (1994) Phase I trial of 3-hour infusion of paclitaxel with or without granulocyte colony-stimulating factor in patients with advanced cancer. J Clin Oncol 12:241–248
Schuchter LM, Hensley ML, Meropol NJ, Winer EP (2002) 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 20:2895–2903
Smith RJ, Wilmore DW (1990) Glutamine nutrition and requirements. JPEN J Parenter Enteral Nutr 14:94S–99S
Strumberg D, Brugge S, Korn MW et al (2002) Evaluation of long-term toxicity in patients after cisplatin-based chemotherapy for non-seminomatous testicular cancer. Ann Oncol 13:229–236
Tasmuth T, Hartel B, Kalso E (2002) Venlafaxine in neuropathic pain following treatment of breast cancer. Eur J Pain 6:17–24
Vahdat L, Papadopoulos K, Lange D et al (2001) Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Clin Cancer Res 7:1192–1197
van der Hoop RG, Vecht CJ, van der Burg ME et al (1990) Prevention of cisplatin neurotoxicity with an ACTH(4–9) analogue in patients with ovarian cancer. N Engl J Med 322:89–94
van Gerven JM, Hovestadt A, Moll JW et al (1994) The effects of an ACTH (4–9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial. J Neurol 241:432–435
Wilson RH, Lehky T, Thomas RR (2002) Acute oxaliplatin-induced peripheral nerve hyperexcitability. J Clin Oncol 20:1767–1774
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ocean, A.J., Vahdat, L.T. Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies. Support Care Cancer 12, 619–625 (2004). https://doi.org/10.1007/s00520-004-0657-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00520-004-0657-7